Amblyopia affects 2% of Americans and is a developmental visual disorder, usually involving poor acuity in one eye. Amblyopia has been well studied behaviorally in humans, and animal models of amblyopia have been developed. However, knowledge of the human neural substrates and mechanisms that underlie the disorder is incomplete. The long-term goal is to develop better treatment strategies for children and adults diagnosed with the two types of amblyopia, called anisometropic and strabismic. The objective of this application is to characterize the functional organization of visual cortex in adult subjects with amblyopia. The central hypothesis is that amblyopia is associated with abnormal patterns of neural activity in particular visual cortical areas, and possibly other brain regions, detected during specific visual tasks measured with functional magnetic resonance imaging (fMRI). By measuring the physiological response of multiple defined visual areas in amblyopic subjects for the first time, we can evaluate the competing accounts of amblyopia, and possibly distinguish the subtypes. The specific aims are: (1.) Relate the monocular foveal contrast sensitivity of amblyopic eyes, fellow eyes and normal eyes to the fMRI signal in defined visual areas in adults with strabismic or anisometropic amblyopia and control subjects. (2.) Measure both cooperative and suppressive binocular interactions on contrast sensitivity psychophysically and physiologically with fMRI in multiple visual cortical areas in these same subjects. This team offers a rare combination of expertise in fMRI, clinical visual assessment, and medical treatment of eye disorders. The methodological approach is appropriate for describing the heterogeneity of amblyopia because detailed maps of brain activation in individual subjects will be produced. This project is innovative because a new, noninvasive tool will be applied to understand the neural mechanisms of a prevalent visual disorder. By showing how neural deficits vary at different stages of visual processing it will be possible to postulate the neural sites of the behavioral loss in amblyopia. In addition, valuable descriptions of how abnormal early sensory experience rearranges plastic neural circuits in the human brain will be provided. In the future, it is possible that amblyopic subjects' treatment may be modified based on the degree to which fMRI activity patterns are normalized, enabling interactive treatment strategies that may greatly reduce the visual impairments in subjects with amblyopia. [unreadable] [unreadable] [unreadable]